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$6 Million Grant from Fondation Leducq for Lymphatic Vascular Study

December 13, 2011, Volume 58, No. 15


Mark L. Kahn, professor of medicine, Perelman School of Medicine at the University of Pennsylvania, received a five-year, $6 million grant from Paris-based Fondation Leducq to study lymphatic vascular defects and their contribution to common human cardiovascular diseases. Dr. Kahn and his lab team, including Dr. Zhiying Zou, Paul Hess, Dr. Zoltan Jakus, and Patty Mericko, lead the North American contingent of an international group that includes two other American and three European academic institutions.

The lymphatic vascular system comprises a large vascular network that regulates fluid balance, transports fats and coordinates immune responses in the body. The lymphatic system is poorly understood compared to the blood vascular system and its role in human vascular diseases is relatively unexplored. The project brings together the major labs investigating lymphatic vascular biology to understand the impact of lymphatic dysfunction on cardiovascular disease and to develop new therapies for lymphatic vascular diseases.

Blood vessels deliver nutrients and oxygen to tissues. Lymph fluid, which is pushed out of blood vessels and bathes the tissues, is drained by lymph vessels that transport the fluid from the tissues back into the cardiovascular system.  In addition to maintaining tissue fluid balance, lymph vessels absorb ingested fats from the intestines and coordinate immune and inflammation responses. There is crosstalk between lymph vessels and fat (adipose) tissue, suggesting a possible link between lymph vessel dysfunction, obesity and inflammation. Lymph vessels are also located in the outer layer (adventitia) of large arteries, where their dysfunction may be important in arterial pathologies such as atherosclerosis and thrombosis. 

The largely unexplored relationship between lymph vessels, obesity and cardiovascular disease is the focus of this network of nine total members from Finland, Germany, Switzerland and the United States, led by Drs. Kahn and Alitalo. The network will study mouse models and human patients to determine the molecular and cellular mechanisms by which lymph vessel dysfunction leads to disease. For instance, investigators will study how lymph vessels and fat cells communicate with each other; how lymph fluid modulates fat cell growth and activity; how fat cells react to inflammation mediated through lymph vessels; and how lymph vessel dysfunction modifies metabolic traits in patients. The network will determine whether lymph vessels represent a beneficial exit route for lipids and inflammatory cells from atherosclerotic plaques; whether the cells that line the interior surface of lymph vessels, like those of blood vessels, can regulate platelet activity and clot formation; and whether manipulation of the lymph vessel growth could be beneficial in heart failure.

The network unites leading laboratories in lymph vessel biology to find novel approaches to the prevention and treatment of obesity and cardiovascular disease.

Almanac - December 13, 2011, Volume 58, No. 15